âBrush-Firstâ Method for the Parallel Synthesis of Photocleavable

Subscriber access provided by FONDREN LIBRARY, RICE UNIVERSITY

Article

A “brush-first” method for the parallel synthesis of photocleavable, nitroxide-labeled PEG star polymers Jenny Liu, Alan O. Burts, Yongjun Li, Aleksandr V. Zhukhovitskiy, Maria Francesca Ottaviani, Nicholas J Turro, and Jeremiah A. Johnson J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja3067176 • Publication Date (Web): 06 Sep 2012 Downloaded from http://pubs.acs.org on September 8, 2012

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Journal of the American Chemical Society is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

A “brush-first” method for the parallel synthesis of photocleavable, nitroxide-labeled PEG star polymers Jenny Liu,1,# Alan O. Burts,1,# Yongjun Li,2 Aleksandr V. Zhukhovitskiy,1 M. Francesca Ottaviani,3 Nicholas J. Turro,2 and Jeremiah A. Johnson1,* Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Department of Chemistry, Columbia University, New York, New York 10027 Department of Earth, Life and Environment Sciences. University of Urbino, 61029 Urbino -‐ Italy ROMP, arm-‐first, graft-‐through, PEG, star polymer, brush polymer, nanoparticle, photodegradable Supporting Information Placeholder ABSTRACT: We describe the parallel, one-‐pot synthesis of core-‐photocleavable, poly(norbornene)-‐co-‐ poly(ethylene glycol) (PEG) brush-‐arm star polymers (BASPs) via a route that combines the “graft-‐through” and “arm-‐first” methodologies for brush polymer and star pol-‐ ymer synthesis, respectively. In this method, ring-‐ opening metathesis polymerization (ROMP) of a nor-‐ bornene-‐PEG macromonomer (MM) generates small liv-‐ ing brush initiators. Transfer of various amounts of this brush initiator to vials containing a photocleavable bis-‐ norbornene crosslinker yielded a series of water-‐soluble BASPs with low polydispersities and molecular weights that increased geometrically as a function of the amount of bis-‐norbornene added. The BASP cores were cleaved upon exposure to ultraviolet light; the extent of photo-‐ disassembly depended on the amount of crosslinker. EPR spectroscopy of nitroxide labeled BASPs was used to probe differences between the BASP core and surface en-‐ vironments. We expect that BASPs will find applications as easy-‐to-‐synthesize stimuli-‐responsive core-‐shell nanostructures.

Introduction. The advent of efficient, functional-‐ group-‐tolerant polymerization reactions has revolution-‐ ized the synthesis of tailored macromolecules with pre-‐ cisely defined nanoscopic features.1,2 Ring-‐opening me-‐ tathesis polymerization (ROMP) is one of the most pow-‐ erful ways to make functional polymers in a controlled fashion.3-‐5 Recently, ROMP catalyzed by 3rd generation Grubbs catalyst6 (1) has been applied to the synthesis of bottle-‐brush,7-‐9 bivalent-‐bottle-‐brush,10-‐13 and dendronized polymers14 via a “graft-‐through” strategy whereby func-‐ tional norbornene macromomoners (MMs) are polymer-‐ ized directly. The synthesis of functional polymeric nanostructures can be greatly simplified via the graft-‐ through approach: all the functionality of the desired nanostructure can be built into MMs.15 Graft-‐through polymerization of these multifunctional MMs generates

polymers of tunable size and functionality for screening in an application of interest. Inefficient polymer modifi-‐ cation reactions are avoided; synthetic efficiency is in-‐ creased. In this report, we seek to broaden the utility of graft-‐ through polymerization via combination with the arm-‐ first technique for star polymer synthesis.16-‐18 In a typical arm-‐first polymerization, linear, end-‐functional polymers (i.e., “arms”) are crosslinked via copolymerization with a multifunctional monomer or “crosslinker.”17 Crosslinking can be initiated between preformed, end-‐functional ma-‐ croinitiators (MIs), MMs, or in situ between living poly-‐ mer chains. The arm-‐first method was first used in the context of anionic polymerization,16,17 and has since been applied to a number of controlled radical polymerization processes18-‐33 and ROMP.34-‐37 Regardless of the polymeri-‐ zation method used, the mechanism of star formation involves a balance of kinetically-‐limited “star+star” and “star+linear” coupling reactions that ultimately defines the structure, size, and uniformity of the final star prod-‐ uct.38 In a pair of seminal reports,34,35 Schrock and coworkers showed that addition of bis-‐olefin crosslinkers to living ROMP reactions led to polynorbornene-‐based star poly-‐ mers with low polydispersities (PDIs) and ~20-‐175 kDa molecular weights (MWs). This basic strategy has since been employed for the preparation of a wide array of functional materials. For example, Buchmeiser has re-‐ ported several bis-‐olefin crosslinked “polymer monoliths” whose functionalities are defined by the choice of mono-‐ mers and crosslinkers.39-‐47 These microparticulate mate-‐ rials have myriad applications as scaffolds for tissue engi-‐ neering, separation media, and supported catalysis. Otani has used Schrock’s Mo(CHCMe2Ph)(N-‐2,6-‐ Pr2C6H3)(OtBu)2 catalyst to initiate ROMP of norbornene followed by addition of a bis-‐olefin crosslinker to generate polynorbornene stars with masses approaching 200 kDa and PDI values ranging from ~1.2-‐1.5.37 In this work, an-‐ other portion of monomer was added after crosslinking to initiate linear polymer growth from the star cores fol-‐ i

ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

lowed by surface functionalization with aldehyde deriva-‐ tives via a Wittig-‐like chain transfer process. The same group later used this approach to generate glycosylated star polymers with terminal fluorophores via use of a nor-‐

Page 2 of 8

bornene-‐galactose monomer and quenching with pyrene-‐ carboxaldehyde.36 Nomura recently reported the synthe-‐ sis of oligo(thiophene)48-‐ and pyridine49-‐coated star pol-‐ ymers via this same multi-‐step strategy.

Figure 1. Synthesis of PEG BASPs via graft-‐through ROMP of MM 2 initiated by 1, followed by arm-‐first crosslinking with 3. The nitrobenzyloxycarbonyl (NBOC) cores of these BASPs degrade under ultraviolet (UV) light. The above arm-‐first ROMP examples are related in that they utilize small-‐molecule monomers to generate MIs, which are ultimately crosslinked to form star polymers. As a result, the ratio of star arms to initiation sites (de-‐ fined here as m) equals 1 during the key star formation process (the final value of m becomes 2 if a second mon-‐ omer is added to initiate arm growth from the core). In related arm-‐first atom transfer radical polymerization (ATRP) reactions, Matyjaszewski and coworkers have shown that increasing m via use of MMs and small mole-‐ cule initiators rather than MIs reduces star+star coupling and leads to more homogeneous star polymer products.50 Subsequent work from the Matyjaszewski group has shown that this basic concept is quite general for arm-‐ first ATRP; several impressive, multi-‐functional star pol-‐ ymers have been prepared via arm-‐first ATRP coupling of MMs.18,22,51,52 To our knowledge, arm-‐first MM crosslinking has not been applied in the context of ROMP. In principle, this strategy would enable synthesis of multi-‐functional star polymers bearing moieties that are incompatible with radical polymerization mechanisms (e.g., persistent radi-‐ cals like nitroxides). Furthermore, surface or core func-‐ tionalized star polymers and miktoarm star polymers could be prepared via arm-‐first crosslinking of appropri-‐ ate telechelic or branched MMs.10-‐13,53 Results and Discussion. In Matyjaszewski’s work, (meth)acrylate-‐terminated MMs, an alkyl bromide initia-‐ tor, crosslinker (e.g., divinylbenzene), and copper catalyst are typically combined at the outset of polymerization. As a result, star cores are formed rapidly via a statistical combination of star+star and star+linear reactions be-‐ tween MM, crosslinker, and newly formed stars. Unreact-‐ ed MM is always present in the reaction medium. At later stages of the reaction, when large star polymers have formed, the rate of star+star coupling is diminished due to steric interactions and the only viable star growth

pathway is chain-‐like star+linear coupling between unre-‐ acted MMs and living star cores. When we attempted the same method in the context of ROMP using poly(ethylene glycol) (PEG) MM 2 and pho-‐ to-‐cleavable crosslinker 3 (Figure 1) we invariably ob-‐ tained materials with very high MW and PDI values (Fig-‐ ure S1). This result suggested that ROMP of 3 was too fast to afford control over the arm-‐first process; 2 was not in-‐ corporated into the growing star polymer quickly enough to preclude rapid crosslinking. We envisioned an alternative approach to controlling m: rather than combine MM and crosslinker at the outset, it should be possible to grow short, living “brush initia-‐ tors” (BI) via homopolymerization of MM (Figure 1, first step), followed by addition of N equivalents of crosslinker (Figure 1, second step) to generate star polymers wherein the star polymer arms are themselves brush polymers (i.e., “brush-‐arm star polymers,” BASPs). In this novel approach, m is the degree of polymerization of the BI, and there is no free MM in the reaction mixture; star growth can only occur via star+star coupling. Here we demonstrate that this “brush-‐first” strategy is useful for the parallel synthesis of degradable PEG BASPs over a wide range of nanoscopic sizes with tunable sur-‐ face and core functionalities. We uncover a novel geo-‐ metric star growth mechanism that yields homogeneous BASPs whose sizes depend on brush length (m) and the amount of crosslinker (N). We demonstrate that surface and core functionalization can be readily achieved via use of telechelic or branched MMs, respectively: subsequent chain transfer or growth of new arms is not required. Furthermore, use of a photo-‐cleavable crosslinker (e.g., 3) facilitates BASP degradation in response to ultraviolet (UV) light (Figure 1, third step). This unique combination of synthetic ease and functional versatility will make brush-‐first BASP synthesis a broadly useful methodology for nanoparticle synthesis.


Page 3 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 2. A. Differential mass GPC traces of N = 10, 15, and 20 BASPs after 4 h crosslinking in THF. Inset: transmission electron micrograph of N = 20 BASP. B. Refractive index GPC traces for BASPs with N = 10 -‐ 40. Unreacted MM and B1 are labeled (*). Mw values increased geometrically with N. C. Log2 plot of Mw versus N for the BASP series from part B. Line-‐ ar fitting produces equation 1, which relates BASP Mw to N. Synthesis of BASPs. To test the viability of brush-‐first BASP synthesis via ROMP, one equivalent of catalyst 1 was added to 10 equivalents of MM 2 in tetrahydrofuran (THF) to form a living brush initiator with DP = 10. After complete consumption of 2, ~10 min, aliquots of the polymerization mixture were added to vials that con-‐ tained 10, 15, and 20 equivalents of crosslinker 3. After 4 h the reactions were quenched with ethyl vinyl ether and solvent was removed in vacuo. The absolute MW of each crude BASP was obtained by gel permeation chromatography (GPC) coupled with a multi-‐angle laser light scattering (MALLS) detector. Fig-‐ ure 2A shows differential weight fraction plots for the set of N = 10, 15, and 20 BASPs. As expected, the brush initia-‐ tor (B1) possessed a low PDI and a weight average MW (Mw) of 28.5 kDa (DP ~ 9, black trace). The N = 10 sample showed multiple mass distributions. The N = 15 and N = 20 samples possessed monomodal MW distributions with Mw values corresponding to ~B16 and ~B32, respectively. As N increased by 5 the Mw of the resulting BASP dou-‐ bled. Intrigued by these results, we next examined a wider range of N values and an alternative ROMP solvent (CH2Cl2, DCM) to verify if this observed mass doubling was reproducible over a wider range of N under varied conditions. Brush-‐first reactions were performed with N values ranging from 10 to 40 in increments of 5. Cross-‐ linking was allowed to proceed for 6 h to ensure maximal conversion. GPC analysis of the crude BASPs showed monomodal MW distributions for all N values tested (Figure 2B), and very high conversions (unreacted 2 and B1, marked with red asterisk in Figure 2B, are present in less than 3% for all cases). The Mw values for this series ranged from 149 kDa (when N = 10) to 8.11 MDa (when N = 40). With each increase of N by five the BASP Mw dou-‐ bled; a log2 plot of Mw versus N is linear (Figure 2C). Fit-‐ ting of these data provides equation 1, which allows pre-‐ diction of Mw given N for this system.

Figure 3. A-‐C. Proposed mechanism for geometric BASP formation via the “brush-‐first” method. Mechanistic hypothesis. To explain the observed ge-‐ ometric MW increase we propose the mechanism depict-‐ ed in Figure 3. In Stage I (Figure 3A), graft-‐through polymerization generates a living brush polymer with DP = m. Addition of N equivalents of crosslinker gives a liv-‐ ing “primary brush initiator” (B1). In contrast to the Matyjaszewski method, the MM is consumed in the graft-‐ through step; the ratio of arms to initiator is large (m), but the only remaining reaction pathway for B1 is star-‐star coupling (Stage II, Figure 3B). If all BASPs, Bx, couple



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

with equal affinity the reaction is classical step-‐growth; the PDI approaches 2.0 with conversion.54 Low PDIs can be obtained if BASP coupling is inhibited with increased size.55,56 In Stage II, B1+B1 coupling to generate dimer B2 is the most viable reaction from a kinetic standpoint. If k1+2 > kx+2x. We hypothesize that the steric bulk of brush polymer arms obtained via the brush-‐first method is key to geometric growth, however, this mecha-‐ nism may be operative in many of the arm-‐first polymeri-‐ zation examples described in the preceding section. The-‐ se reports never explored a wide range of N values; per-‐ haps iterative dimerization was simply overlooked.

Page 4 of 8

sample for each m value (blue traces) was multimodal suggesting that 10 equivalents of 3 is not sufficient to af-‐ ford control in this system. However, uniform BASPs were realized for most N = 15 and 20 values (regardless of m). A plot of Mw versus N for the various m values tested shows that as m increases, the BASP mass decreases. When m = 7 and N = 20, B64 is obtained. When m is in-‐ creased to 11 or 14, with N held at 20, B32 is obtained. The same trend holds for the N = 15 cases. These results demonstrate that decreasing m allows for further dimeri-‐ zation events; smaller B1 species lead to larger BASPs.

Figure 4. A-‐C. GPC traces for m = 7, 11, and 14 BASPs with N = 10, 15, and 20. D. Plot of Mw versus N for various m values. As m increases, the final size of the BASP decreas-‐ es.

Mechanistic studies. If the mechanism proposed in Figure 3 were operative, one would predict that the final values of x for a given BASP would depend on both N and m. In particular, if N is increased the number of available crosslinking sites increases and the overall length of the crosslinker block of B1 increases. These features should increase the BASP core size, reduce steric hindrance, and allow access to larger x values. This trend is evident in Figure 2. In contrast, as brush length (m) is increased we expect that the final BASP x value should decrease due to in-‐ creased steric hindrance. Figures 4A-‐C show GPC traces for BASPs formed under identical conditions to those used in Figure 2A (THF solvent, 4h crosslinking) using N = 10, 15, and 20 and m values of 7, 11, and 14. The N = 10

Figure 5. A-‐B. Kinetic analysis of BASP formation. Di-‐ merized Bx species are clearly visible throughout the crosslinking reaction. N determines the final average x value.


4

Page 5 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 6. A-‐D. GPC analysis of BASP degradation for a variety of N and m values. E. Possible intramolecular cyclization reactions that increase the number of NBOC groups that must be cleaved for complete BASP degradation. Next we performed kinetic analyses for N = 15 and 20 (m = 10) BASP formation reactions. For these studies, small samples were taken from a crosslinking reaction, quenched with ethyl vinyl ether, and directly analyzed by GPC. If the mechanism from Figure 3 is correct, it should be possible to trap various dimerized Bx products over the course of the crosslinking reaction. Furthermore, B1 should be consumed at early stages of the reaction. The results for the N = 15 case are shown in Figure 5A. After 9 min (red trace) there is a convoluted mixture of Bx values that contains B1 and B2 fractions, along with some B3 and B4. After 30 min (purple trace), B1 is completely con-‐ sumed and peaks for B2, B4, and B8 are clearly visible as major components. After 240 min these smaller Bx values converge to give product enriched with B16. In the N = 20 case (Figure 5B), dimerized products are observed in the earliest time point (3.5 min), and B1 is consumed within 11 min. It appears that increasing N leads to faster crosslinking in earlier stages, which sup-‐ ports the hypothesis that increased N reduces steric hin-‐ drance. Here, at 60 min (maroon trace) the system con-‐ sists almost entirely of B16 (240 min needed for the N = 15 case). After 120 min, there is a ~1:1 mixture of B16 and B32, and finally, after 240 min B32 is obtained. GPC analysis of both reactions after 24 h showed no increase in mass or change in PDI. Taken together, these data provide strong support for the mechanism depicted in Figure 3. Iterative dimerization events occur until the reaction system set-‐ tles on an optimal persistent x value. BASP degradation studies. Crosslinker 3 possesses a NBOC group known to cleave upon UV irradiation.57 The concept of embedding NBOC groups within polymeric structures has become a common strategy for the synthe-‐ sis of photodegradable materials.58-‐61 As described in Fig-‐ ure 1, complete cleavage of NBOC groups in the core of BASPs should regenerate the parent brush polymers with short blocks of NBOC cleavage products appended to the chain ends (the latter are neglected in Figure 3 for clarity).

Figure 6 shows GPC traces of various BASPs before and after UV irradiation (365 nm for 4 h in THF). In the N = 15, m = 11 case the degradation reaction regenerates the parent brush polymer cleanly (Figure 6A). However, when N is increased to 20 and m held constant at 11 (Fig-‐ ure 6B), a mixture of Bx cleavage products are obtained; degradation does not reach 100% conversion. Similar results were obtained when N was held at 15 and m de-‐ creased to 7 (Figure 6C), and when both m and N were increased (Figure 6D). As described in the previous sec-‐ tion, increasing N and decreasing m both lead to larger BASPs. The BASP samples studied in Figures 6A, 6B, 6C, and 6D have Mw values of 588 kDa (B16), 1.2 MDa (B32), 850 kDa (B32), and 926 kDa (B16), respectively. Given the Bx value for each sample, the number of NBOC groups per BASP can be easily calculated as N • Bx; the BASP from Figure 6A has ~240 NBOC groups, while the BASPs from Figures 6B, 6C, and 6D have 640, 480, and 320 NBOC groups, respectively. We hypothesize that this variation in the number of NBOC groups per BASP defines the overall extent of deg-‐ radation. Only the sample with the fewest NBOC groups reached complete degradation. Cyclization reactions – i.e., intramolecular crosslinking between Ru and unreact-‐ ed norbornene groups within the same brush or BASP core (Figure 6E) -‐ are likely to occur. Photocleavage of these intramolecular crosslinks would not lead to a de-‐ crease in mass, but instead would manifest itself as an apparent mass increase by GPC due to increased hydro-‐ dynamic volume post-‐cleavage.62,63 As the number of NBOC moieties increases in a given BASP, the number of intramolecular crosslinks increases as well. Though NBOC cleavage is generally a very effi-‐ cient reaction, there appears to be a limit to the number of NBOC groups that can be successfully cleaved in a sin-‐ gle BASP particle. This limit may be due to a small per-‐ centage of side reactions that consume NBOC groups but


5


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

do not lead to cleavage, or competing light absorption between unreacted NBOC groups and nitrosobenzalde-‐ hyde cleavage products.

Figure 7. A-‐B. TEM images of BASPs before and after UV irradiation. TEM images of N = 15 and 20 (m = 14) BASPs before and after irradiation (Figure 7) agree with the GPC results from Figure 6. Figure 7A shows the N = 20 particles. UV irradiation for 30 min in H2O led to a decrease in size from 86 nm to 24 nm. For the N = 15 case (Figure 7B), the starting particles were much smaller (27 nm), and irradia-‐ tion led to formation of 12 nm particles.

Figure 8. Aqueous volume-‐average DLS histograms be-‐ fore and after BASP degradation. DLS correlation func-‐ tions were fitted using the CONTIN algorithm. Dynamic light scattering (DLS) was also used to study photoinitiated BASP disassembly. Irradiation of aqueous BASP solutions for 10 min led to observed decreases in hydrodynamic diameter Dh. The N = 15 BASP had a Dh of 24 nm before irradiation (green histogram, Figure 8), while irradiation yielded 8 nm particles. In the N = 40 case, 28 nm degradation products are obtained.

Page 6 of 8

DLS. This observation may be due to the fact that the BASP core is very hydrophobic; the BASP structure is col-‐ lapsed in water to avoid interactions between the core and the solvent.

Figure 9. Nitroxide MMs 4 and 5 allow for selective pe-‐ riphery and core BASP labeling, respectively. The rate of nitroxide quenching with PEG-‐PhNHNH2 depends on the nitroxide location within the BASP nanostructure. To probe this hypothesis in more detail, and demon-‐ strate that surface and core functional BASPs could be easily generated in one pot, 5% of nitroxide-‐labeled MMs 4 and 5 were incorporated into BASPs with N = 15 (Figure 9). Use of telechelic MM 4 leads to nitroxide groups at the BASP surface while use of branched MM 5 leads to BASPs with core-‐bound nitroxides. The GPC traces for both the peripherally-‐labeled (p) and core-‐labeled (c) samples indicated very high MM conversion and mono-‐ modal MW distributions (Figure 10A); the use of nitrox-‐ ides and branched MMs does not inhibit BASP formation. DLS analysis confirms that the hydrodynamic radii of p and c decrease under UV irradiation (Figure 10B). Electron paramagnetic resonance (EPR) spectroscopy is a convenient method for studying nitroxide-‐labeled mac-‐ romolecular systems; the EPR spectrum is sensitive to environmental factors such as polarity, viscosity, and ste-‐ ric hindrance.53,64,65 Figure 10C shows EPR spectra for BASPs c and p before and after irradiation. The increased spectral broadening for c compared to p is indicative of the hindered environment experienced by the core-‐bound nitroxide label. This steric hindrance is captured quanti-‐ tatively by an increased correlation time for rotational diffusion, τ, which is 0.03 ns for p and 0.95 ns for c. UV degradation leads to no change in the spectrum for p; a small but significant sharpening (labeled *, Figure 10C) is observed for c. These results suggest that nitroxides at the BASP surface are equally shielded before and after degradation while core-‐nitroxides experience less steric hindrance after irradiation (depicted schematically in Figure 9).

These BASP particles are highly soluble in water, and they do not aggregate significantly with time. However, BASPs of similar Mw always appear larger by TEM than


6

Page 7 of 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society Supporting Information. Supplemental figures, details regarding EPR analysis, detailed synthetic procedures and spectral data. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION J. Liu and A. O. Burts contributed equally to this work.

Corresponding Author [email protected]

ACKNOWLEDGMENT

Figure 10. A. GPC traces for peripherally-‐ (p) and core-‐ (c) labeled BASPs. B. DLS analysis of p and c. C. EPR spectra before and after UV irradiation. D. Quenching kinetics. EPR active nitroxides are reduced by phenyl hydrazine derivatives to generate EPR silent hydroxylamines. This reaction “quenches” the EPR signals; the rate of quench-‐ ing depends on the steric hindrance experienced by the hydrazine reagent. We previously demonstrated that quenching rates are faster for peripherally-‐labeled poly(lactide) brush polymers in organic solvents com-‐ pared to core-‐labeled analogs.53 Here we describe the first application of this method to aqueous BASP systems. To explore quenching under these conditions, water soluble, polymeric quencher Q was designed (Figure 9). Quench-‐ ing was performed under pseudo-‐first order conditions with excess Q. We found that quenching of the EPR sig-‐ nal of surface-‐labeled p was 3X faster than for core-‐ labeled c, which confirms that the BASP core is sterically shielded from external reagents (Figure 10D). Shielding of hydrophobic materials within a star or dendritic core has been exploited for one-‐pot dual catalysis66 and drug deliv-‐ ery applications.67,68 Ongoing studies are aimed toward using nitroxide labeled BASPs as supported oxidation catalysts. This work represents the first demonstration of brush-‐ first crosslinking to give brush-‐arm star polymers (BASPs). The presented PEG BASPs grow geometrically with increased crosslinker amount, which allows facile access to nanoparticles with a wide range of diameters. UV irradiation leads to rapid BASP degradation; the over-‐ all extent of degradation depends on the number of NBOC groups in the BASP core. The functional group tolerance of catalyst 1 was exploited for the synthesis of nitroxide-‐labeled BASPs. EPR analysis confirmed that the BASP core and periphery have different environmental features and reactivity. We are currently applying this novel “brush-‐first” method for the one-‐pot parallel syn-‐ thesis of multi-‐functional nanostructures for a variety of applications.

ASSOCIATED CONTENT

We thank the Massachusetts Institute of Technology De-‐ partment of Chemistry and the DoD NDSEG program (grad-‐ uate fellowship for A. Zhukhovitskiy) for support of this work. We also thank Dr. P. Patel for advice related to prepa-‐ ration of Q, and Prof. M. Movassaghi for use of his group’s Rayonet photoreactor.

REFERENCES (1) Hawker, C. J.; Wooley, K. L. Science (Washington, DC, U. S.) 2005, 309, 1200-1205. (2) Yagci, Y.; Tasdelen, M. A. Prog. Polym. Sci. 2006, 31, 1133-1170. (3) Handbook of Metathesis; Wiley-VCH: Weinheim, 2003; Vol. 3. (4) Bielawski, C. W.; Grubbs, R. H. Prog. Polym. Sci. 2007, 32, 1-29. (5) Leitgeb, A.; Wappel, J.; Slugovc, C. Polymer 2010, 51, 2927-2946. (6) Love, J. A.; Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew. Chem., Int. Ed. 2002, 41, 4035-4037. (7) Xia, Y.; Kornfield, J. A.; Grubbs, R. H. Macromolecules (Washington, DC, U. S.) 2009, 42, 3761-3766. (8) Li, Z.; Zhang, K.; Ma, J.; Cheng, C.; Wooley, K. L. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 5557-5563. (9) Le, D.; Montembault, V.; Soutif, J. C.; Rutnakornpituk, M.; Fontaine, L. Macromolecules (Washington, DC, U. S.) 2010, 43, 5611-5617. (10) Johnson, J. A.; Lu, Y.-Y.; Burts, A. O.; Lim, Y.-H.; Finn, M. G.; Koberstein, J. T.; Turro, N. J.; Tirrell, D. A.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 559-566. (11) Johnson, J. A.; Lu, Y. Y.; Burts, A. O.; Xia, Y.; Durrell, A. C.; Tirrell, D. A.; Grubbs, R. H. Macromolecules (Washington, DC, U. S.) 2010, 43, 10326-10335. (12) Li, Y. K.; Zou, J.; Das, B. P.; Tsianou, M.; Cheng, C. Macromolecules 2012, 45, 4623-4629. (13) Li, Y.; Themistou, E.; Zou, J.; Das, B. P.; Tsianou, M.; Cheng, C. ACS Macro Lett. 2012, 1, 52-56. (14) Boydston, A. J.; Holcombe, T. W.; Unruh, D. A.; Frechet, J. M. J.; Grubbs, R. H. J. Am. Chem. Soc. 2009, 131, 5388-5389. (15) Hadjichristidis, N.; Pitsikalis, M.; Iatrou, H.; Pispas, S. Macromol. Rapid Commun. 2003, 24, 979-1013. (16) Kohler, A.; Koessler, I.; Zilliox, J. G.; Polacek, J.; Rempp, P. Eur. Polym. J. 1972, 8, 627-&. (17) Worsfold, D. J.; Zilliox, J. G.; Rempp, P. Can. J. Chem. 1969, 47, 3379-&. (18) Matyjaszewski, K.; Tsarevsky, N. V. Nature Chem. 2009, 1, 276-288. (19) Xia, J. H.; Zhang, X.; Matyjaszewski, K. Macromolecules 1999, 32, 4482-4484. (20) Gao, H. F.; Matyjaszewski, K. Macromolecules 2006, 39, 3154-3160. (21) Gao, H.; Matyjaszewski, K. J. Am. Chem. Soc. 2007, 129, 11828-11834. 7



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(22) Gao, H. F.; Matyjaszewski, K. Macromolecules 2008, 41, 4250-4257. (23) Dai, F. Y.; Sun, P.; Liu, Y. J.; Liu, W. G. Biomaterials 2010, 31, 559-569. (24) Goh, T. K.; Yamashita, S.; Satoh, K.; Blencowe, A.; Kamigaito, M.; Qiao, G. G. Macromol. Rapid Commun. 2011, 32, 456-461. (25) Koda, Y.; Terashima, T.; Nomura, A.; Ouchi, M.; Sawamoto, M. Macromolecules 2011, 44, 4574-4578. (26) Terashima, T.; Motokawa, R.; Koizumi, S.; Sawamoto, M.; Kamigaito, M.; Ando, T.; Hashimoto, T. Macromolecules 2010, 43, 8218-8232. (27) Gao, H. F.; Tsarevsky, N. V.; Matyjaszewski, K. Macromolecules 2005, 38, 5995-6004. (28) Bosman, A. W.; Vestberg, R.; Heumann, A.; Frechet, J. M. J.; Hawker, C. J. J. Am. Chem. Soc. 2003, 125, 715-728. (29) Bosman, A. W.; Heumann, A.; Klaerner, G.; Benoit, D.; Frechet, J. M. J.; Hawker, C. J. J. Am. Chem. Soc. 2001, 123, 6461-6462. (30) Adkins, C. T.; Harth, E. Macromolecules 2008, 41, 34723480. (31) Cheng, F.; Bonder, E. M.; Doshi, A.; Jakle, F. Polymer Chemistry 2012, 3, 596-600. (32) Zheng, G. H.; Pan, C. Y. Polymer 2005, 46, 2802-2810. (33) Blencowe, A.; Tan, J. F.; Goh, T. K.; Qiao, G. G. Polymer 2009, 50, 5-32. (34) Saunders, R. S.; Cohen, R. E.; Wong, S. J.; Schrock, R. R. Macromolecules 1992, 25, 2055-2057. (35) Bazan, G. C.; Schrock, R. R. Macromolecules 1991, 24, 817-823. (36) Otani, H.; Fujita, S.; Watanabe, Y.; Fujiki, M.; Nomura, K. Macromol. Symp. 2010, 293, 53-57. (37) Nomura, K.; Watanabe, Y.; Fujita, S.; Fujiki, M.; Otani, H. Macromolecules 2009, 42, 899-901. (38) Gao, H. F. Macromol. Rapid Commun. 2012, 33, 722-734. (39) Bandari, R.; Buchmeiser, M. R. Catal. Sci. Technol. 2012, 2, 220-226. (40) Weichelt, F.; Lenz, S.; Tiede, S.; Reinhardt, I.; Frerich, B.; Buchmeiser, M. R. Beilstein J. Org. Chem. 2010, 6, 1199-1205, No 1137. (41) Weichelt, F.; Frerich, B.; Lenz, S.; Tiede, S.; Buchmeiser, M. R. Macromol. Rapid Commun. 2010, 31, 1540-1545. (42) Mayr, M.; Mayr, B.; Buchmeiser, M. R. Angew. Chem., Int. Ed. 2001, 40, 3839-3842. (43) Buchmeiser, M. R.; Kroll, R.; Wurst, K.; Schareina, T.; Kempe, R.; Eschbaumer, C.; Schubert, U. S. Macromol. Symp. 2001, 164, 187-196. (44) Buchmeiser, M. R.; Wurst, K. J. Am. Chem. Soc. 1999, 121, 11101-11107. (45) Sinner, F.; Buchmeiser, M. R.; Tessadri, R.; Mupa, M.; Wurst, K.; Bonn, G. K. J. Am. Chem. Soc. 1998, 120, 2790-2797. (46) Buchmeiser, M. R.; Seeber, G.; Bonn, G. K.; Bertsch, T. J. Chromatogr., A 1998, 809, 121-129.

Page 8 of 8

(47) Buchmeiser, M. R.; Atzl, N.; Bonn, G. K. J. Am. Chem. Soc. 1997, 119, 9166-9174. (48) Takamizu, K.; Nomura, K. J. Am. Chem. Soc. 2012, 134, 7892-7895. (49) Nomura, K.; Tanaka, K.; Fujita, S. Organometallics 2012, 31, 5074-5080. (50) Gao, H. F.; Ohno, S.; Matyjaszewski, K. J. Am. Chem. Soc. 2006, 128, 15111-15113. (51) Matyjaszewski, K.; Cho, H. Y.; Gao, H. F.; Srinivasan, A.; Hong, J.; Bencherif, S. A.; Siegwart, D. J.; Paik, H. J.; Hollinger, J. O. Biomacromolecules 2010, 11, 2199-2203. (52) Gao, H. F.; Matyjaszewski, K. Macromolecules 2007, 40, 399-401. (53) Xia, Y.; Li, Y. J.; Burts, A. O.; Ottaviani, M. F.; Tirrell, D. A.; Johnson, J. A.; Turro, N. J.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 19953-19959. (54) Flory, P. J. Principles of Polymer Chemistry, 1953. (55) Nanda, V. S.; Jain, S. C. J. Chem. Phys. 1968, 49, 13181320. (56) Cotts, D. B.; Berry, G. C. Macromolecules 1981, 14, 930934. (57) Bochet, C. G. J. Chem. Soc., Perkin Trans. 1 2002, 125142. (58) Johnson, J. A.; Baskin, J. M.; Bertozzi, C. R.; Koberstein, J. T.; Turro, N. J. Chem. Commun. (Cambridge, U. K.) 2008, 3064-3066. (59) Johnson, J. A.; Finn, M. G.; Koberstein, J. T.; Turro, N. J. Macromolecules (Washington, DC, U. S.) 2007, 40, 3589-3598. (60) Kloxin, A. M.; Kasko, A. M.; Salinas, C. N.; Anseth, K. S. Science (Washington, DC, U. S.) 2009, 324, 59-63. (61) Zhao, H.; Sterner, E. S.; Coughlin, E. B.; Theato, P. Macromolecules 2012, 45, 1723-1736. (62) Laurent, B. A.; Grayson, S. M. J. Am. Chem. Soc. 2006, 128, 4238-4239. (63) Bielawski, C. W.; Benitez, D.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 8424-8425. (64) Veksli, Z.; Andreis, M.; Rakvin, B. Prog. Polym. Sci. 2000, 25, 949-986. (65) Jeschke, G. Macromol. Rapid Commun. 2002, 23, 227-246. (66) Helms, B.; Guillaudeu, S. J.; Xie, Y.; McMurdo, M.; Hawker, C. J.; Frechet, J. M. J. Angew. Chem., Int. Ed. 2005, 44, 6384-6387. (67) Lee, C. C.; Gillies, E. R.; Fox, M. E.; Guillaudeu, S. J.; Frechet, J. M. J.; Dy, E. E.; Szoka, F. C. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 16649-16654. (68) Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C.; Margalit, R.; Langer, R. Nat. Nanotechnol. 2007, 2, 751-760.

8 ACS Paragon Plus Environment

âBrush-Firstâ Method for the Parallel Synthesis of Photocleavable

Recommend Documents

âBrush-Firstâ Method for the Parallel Synthesis of Photocleavable